Introns Protect Eukaryotic Genomes from Transcription-Associated Genetic Instability
| Autor: | Vincent Géli, Ana Rita Grosso, Guilhem Janbon, Emeline Coleno, Sérgio F. de Almeida, Amandine Bonnet, Adrien Presle, Sree Rama Chaitanya Sridhara, Abdessamad El-Kaoutari, Benoit Palancade |
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| Přispěvatelé: | Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Faculdade de Medicina [Lisboa], Universidade de Lisboa = University of Lisbon (ULISBOA), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des ARN des Pathogènes fongiques - RNA Biology of Fungal Pathogens, Institut Pasteur [Paris] (IP), This work was supported by CNRS (to B.P.), Fondation ARC pour la Recherche sur le Cancer (to B.P.), Ligue Nationale contre le Cancer (to B.P., fellowship to A.B. and Equipe Labellisée 2014 to V.G.), EMBO (short-term fellowship to A.B.), Cancéropole PACA (fellowship to A.E.), and Fundaçao para a Ciencia e Tecnologia, Portugal (PTDC/BIM-ONC/0016-2014 to S.F.d.A. and IF/00510/2014 to A.R.G.). Bioinformatic and computing support at CRCM was provided by the CRCM Integrative Bioinformatics and Datacentre IT and Scientific Computing platforms., Universidade de Lisboa (ULISBOA), Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Biologie des ARN des Pathogènes fongiques |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Transcription Genetic MESH: Introns [SDV]Life Sciences [q-bio] Candida glabrata mRNA splicing MESH: Genotype 0302 clinical medicine MESH: Structure-Activity Relationship Minor spliceosome Gene Expression Regulation Fungal Databases Genetic DNA Fungal MESH: Candida glabrata MESH: Databases Genetic Genetics Splice site mutation MESH: Genomic Instability Nucleic Acid Heteroduplexes genetic instability MESH: Cryptococcus neoformans Group II intron R-loops MESH: Saccharomyces cerevisiae messenger ribonucleoparticle Phenotype MESH: Nucleic Acid Conformation MESH: Schizosaccharomyces Ribonucleoproteins RNA splicing MESH: Fungal Proteins transcription MESH: Spliceosomes MESH: Gene Expression Regulation Fungal MESH: Computational Biology Spliceosome Genotype intron RNA Splicing Saccharomyces cerevisiae Biology MESH: Phenotype Genomic Instability Cell Line Fungal Proteins Structure-Activity Relationship 03 medical and health sciences mRNP MESH: Nucleic Acid Heteroduplexes Schizosaccharomyces Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Molecular Biology Gene MESH: DNA Damage MESH: Humans MESH: RNA Fungal MESH: Transcription Genetic Intron Computational Biology RNA RNA Fungal [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Cell Biology Introns recombination MESH: Cell Line MESH: DNA Fungal MESH: Ribonucleoproteins 030104 developmental biology Cryptococcus neoformans Spliceosomes Nucleic Acid Conformation MESH: RNA Splicing 030217 neurology & neurosurgery DNA Damage |
| Zdroj: | Molecular Cell Molecular Cell, 2017, 67 (4), pp.608-621.e6. ⟨10.1016/j.molcel.2017.07.002⟩ Molecular Cell, Elsevier, 2017, 67 (4), pp.608-621.e6. ⟨10.1016/j.molcel.2017.07.002⟩ |
| ISSN: | 1097-2765 1097-4164 |
| DOI: | 10.1016/j.molcel.2017.07.002 |
| Popis: | International audience; Transcription is a source of genetic instability that can notably result from the formation of genotoxic DNA:RNA hybrids, or R-loops, between the nascent mRNA and its template. Here we report an unexpected function for introns in counteracting R-loop accumulation in eukaryotic genomes. Deletion of endogenous introns increases R-loop formation, while insertion of an intron into an intronless gene suppresses R-loop accumulation and its deleterious impact on transcription and recombination in yeast. Recruitment of the spliceosome onto the mRNA, but not splicing per se, is shown to be critical to attenuate R-loop formation and transcription-associated genetic instability. Genome-wide analyses in a number of distant species differing in their intron content, including human, further revealed that intron-containing genes and the intron-richest genomes are best protected against R-loop accumulation and subsequent genetic instability. Our results thereby provide a possible rationale for the conservation of introns throughout the eukaryotic lineage. |
| Databáze: | OpenAIRE |
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